Kaempferol Protects Renal Fibrosis through Activating the BMP-7-Smad1/5 Signaling Pathway
Renal interstitial fibrosis (RIF) is a common pathological characteristic associated with end-stage renal disease. However, treatment strategies for RIF are still very limited. In this study, we reported that kaempferol, a classic flavonoid, exhibited strong and widely inhibitory effect on the expre...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2020/03/01, Vol.43(3), pp.533-539 |
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| creator | Ji, Xiaojun Cao, Jing Zhang, Liting Zhang, Zhirui Shuai, Weiwei Yin, Wu |
| description | Renal interstitial fibrosis (RIF) is a common pathological characteristic associated with end-stage renal disease. However, treatment strategies for RIF are still very limited. In this study, we reported that kaempferol, a classic flavonoid, exhibited strong and widely inhibitory effect on the expression of fibrosis related genes in transforming growth factor beta 1 (TGF-β1) treated NRK-52E cells. Further studies revealed that kaempferol inhibited TGF-β1 induced epithelial–mesenchymal transition (EMT) process of NRK-52E cells and improved renal function deterioration and RIF in unilateral ureteral obstruction (UUO) rats. After exploring the underlying mechanisms, we found that kaempferol was able to activate the BMP-7-Smad1/5 pathway, rather than the TGF-β1-Smad2/3 pathway. To further validate these results, DMH1 and BMP-7 knockdown were utilized at the cellular level and the results showed that both methods were able to antagonize the effects of kaempferol on the EMT process of NRK-52E cells induced by TGF-β1. In UUO rats, inhibition of BMP-7 signaling by DMH1 also reversed the effects of kaempferol on renal function decline and RIF. Taken together, our findings demonstrated that kaempferol could be a good candidate for renal fibrosis treatment. |
| doi_str_mv | 10.1248/bpb.b19-01010 |
| format | Article |
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However, treatment strategies for RIF are still very limited. In this study, we reported that kaempferol, a classic flavonoid, exhibited strong and widely inhibitory effect on the expression of fibrosis related genes in transforming growth factor beta 1 (TGF-β1) treated NRK-52E cells. Further studies revealed that kaempferol inhibited TGF-β1 induced epithelial–mesenchymal transition (EMT) process of NRK-52E cells and improved renal function deterioration and RIF in unilateral ureteral obstruction (UUO) rats. After exploring the underlying mechanisms, we found that kaempferol was able to activate the BMP-7-Smad1/5 pathway, rather than the TGF-β1-Smad2/3 pathway. To further validate these results, DMH1 and BMP-7 knockdown were utilized at the cellular level and the results showed that both methods were able to antagonize the effects of kaempferol on the EMT process of NRK-52E cells induced by TGF-β1. In UUO rats, inhibition of BMP-7 signaling by DMH1 also reversed the effects of kaempferol on renal function decline and RIF. Taken together, our findings demonstrated that kaempferol could be a good candidate for renal fibrosis treatment.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b19-01010</identifier><identifier>PMID: 32115512</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>BMP-7 ; Clear cell-type renal cell carcinoma ; End-stage renal disease ; epithelial–mesenchymal transition ; Fibrosis ; Flavonoids ; Kaempferol ; Kidney diseases ; Mesenchyme ; Renal function ; renal interstitial fibrosis ; Signal transduction ; Smad1/5 ; Smad2 protein ; Transforming growth factor-b1</subject><ispartof>Biological and Pharmaceutical Bulletin, 2020/03/01, Vol.43(3), pp.533-539</ispartof><rights>2020 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c702t-b28b645acac629d4186c48b11d94b56c89a02d72a54f28be8a8f1263a4f8d5173</citedby><cites>FETCH-LOGICAL-c702t-b28b645acac629d4186c48b11d94b56c89a02d72a54f28be8a8f1263a4f8d5173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32115512$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ji, Xiaojun</creatorcontrib><creatorcontrib>Cao, Jing</creatorcontrib><creatorcontrib>Zhang, Liting</creatorcontrib><creatorcontrib>Zhang, Zhirui</creatorcontrib><creatorcontrib>Shuai, Weiwei</creatorcontrib><creatorcontrib>Yin, Wu</creatorcontrib><creatorcontrib>aState Key Lab of Pharmaceutical Biotechnology</creatorcontrib><creatorcontrib>College of Life Sciences</creatorcontrib><creatorcontrib>bDepartment of Pharmacy</creatorcontrib><creatorcontrib>Nanjing University</creatorcontrib><creatorcontrib>Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital</creatorcontrib><title>Kaempferol Protects Renal Fibrosis through Activating the BMP-7-Smad1/5 Signaling Pathway</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Renal interstitial fibrosis (RIF) is a common pathological characteristic associated with end-stage renal disease. However, treatment strategies for RIF are still very limited. In this study, we reported that kaempferol, a classic flavonoid, exhibited strong and widely inhibitory effect on the expression of fibrosis related genes in transforming growth factor beta 1 (TGF-β1) treated NRK-52E cells. Further studies revealed that kaempferol inhibited TGF-β1 induced epithelial–mesenchymal transition (EMT) process of NRK-52E cells and improved renal function deterioration and RIF in unilateral ureteral obstruction (UUO) rats. After exploring the underlying mechanisms, we found that kaempferol was able to activate the BMP-7-Smad1/5 pathway, rather than the TGF-β1-Smad2/3 pathway. To further validate these results, DMH1 and BMP-7 knockdown were utilized at the cellular level and the results showed that both methods were able to antagonize the effects of kaempferol on the EMT process of NRK-52E cells induced by TGF-β1. In UUO rats, inhibition of BMP-7 signaling by DMH1 also reversed the effects of kaempferol on renal function decline and RIF. Taken together, our findings demonstrated that kaempferol could be a good candidate for renal fibrosis treatment.</description><subject>BMP-7</subject><subject>Clear cell-type renal cell carcinoma</subject><subject>End-stage renal disease</subject><subject>epithelial–mesenchymal transition</subject><subject>Fibrosis</subject><subject>Flavonoids</subject><subject>Kaempferol</subject><subject>Kidney diseases</subject><subject>Mesenchyme</subject><subject>Renal function</subject><subject>renal interstitial fibrosis</subject><subject>Signal transduction</subject><subject>Smad1/5</subject><subject>Smad2 protein</subject><subject>Transforming growth factor-b1</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpdkM1v1DAQxS0EosvCkSuKxIVLWn8mzrGsaEEt6qqFAydr7Di7XiXx1nZA_e_xNu0iIUtjy_Pzm-eH0HuCTwnl8kzv9akmTYlJXi_QgjBel4IS8RItcENkWREhT9CbGHcY4xpT9hqdMEqIEIQu0K8rsMO-s8H3xTr4ZE2Kxa0doS8unA4-ulikbfDTZlucm-R-Q3LjJl_Z4vP3dVmXdwO05EwUd26THx16a0jbP_DwFr3qoI_23dO-RD8vvvxYfS2vby6_rc6vS5PNpFJTqSsuwICpaNNyIivDpSakbbgWlZENYNrWFATvMmolyI7QigHvZCtIzZbo06y7D_5-sjGpwUVj-x5G66eoKKsaWddY0ox-_A_d-Slk2zMlKiqJzFQ5UyZ_PwbbqX1wA4QHRbA6ZK5y5ipnrh4zz_yHJ9VJD7Y90s8hZ-ByBnLXGej9mHOy_2abWGvne68oplhhzBlmClOhsGDsUBrGJa_yYYlWs9IuJtjY4ygIyZnePhrjTLFDORo8ds0WgrIj-wvJNKj3</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Ji, Xiaojun</creator><creator>Cao, Jing</creator><creator>Zhang, Liting</creator><creator>Zhang, Zhirui</creator><creator>Shuai, Weiwei</creator><creator>Yin, Wu</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20200301</creationdate><title>Kaempferol Protects Renal Fibrosis through Activating the BMP-7-Smad1/5 Signaling Pathway</title><author>Ji, Xiaojun ; Cao, Jing ; Zhang, Liting ; Zhang, Zhirui ; Shuai, Weiwei ; Yin, Wu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c702t-b28b645acac629d4186c48b11d94b56c89a02d72a54f28be8a8f1263a4f8d5173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>BMP-7</topic><topic>Clear cell-type renal cell carcinoma</topic><topic>End-stage renal disease</topic><topic>epithelial–mesenchymal transition</topic><topic>Fibrosis</topic><topic>Flavonoids</topic><topic>Kaempferol</topic><topic>Kidney diseases</topic><topic>Mesenchyme</topic><topic>Renal function</topic><topic>renal interstitial fibrosis</topic><topic>Signal transduction</topic><topic>Smad1/5</topic><topic>Smad2 protein</topic><topic>Transforming growth factor-b1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ji, Xiaojun</creatorcontrib><creatorcontrib>Cao, Jing</creatorcontrib><creatorcontrib>Zhang, Liting</creatorcontrib><creatorcontrib>Zhang, Zhirui</creatorcontrib><creatorcontrib>Shuai, Weiwei</creatorcontrib><creatorcontrib>Yin, Wu</creatorcontrib><creatorcontrib>aState Key Lab of Pharmaceutical Biotechnology</creatorcontrib><creatorcontrib>College of Life Sciences</creatorcontrib><creatorcontrib>bDepartment of Pharmacy</creatorcontrib><creatorcontrib>Nanjing University</creatorcontrib><creatorcontrib>Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ji, Xiaojun</au><au>Cao, Jing</au><au>Zhang, Liting</au><au>Zhang, Zhirui</au><au>Shuai, Weiwei</au><au>Yin, Wu</au><aucorp>aState Key Lab of Pharmaceutical Biotechnology</aucorp><aucorp>College of Life Sciences</aucorp><aucorp>bDepartment of Pharmacy</aucorp><aucorp>Nanjing University</aucorp><aucorp>Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kaempferol Protects Renal Fibrosis through Activating the BMP-7-Smad1/5 Signaling Pathway</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>43</volume><issue>3</issue><spage>533</spage><epage>539</epage><pages>533-539</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>Renal interstitial fibrosis (RIF) is a common pathological characteristic associated with end-stage renal disease. However, treatment strategies for RIF are still very limited. In this study, we reported that kaempferol, a classic flavonoid, exhibited strong and widely inhibitory effect on the expression of fibrosis related genes in transforming growth factor beta 1 (TGF-β1) treated NRK-52E cells. Further studies revealed that kaempferol inhibited TGF-β1 induced epithelial–mesenchymal transition (EMT) process of NRK-52E cells and improved renal function deterioration and RIF in unilateral ureteral obstruction (UUO) rats. After exploring the underlying mechanisms, we found that kaempferol was able to activate the BMP-7-Smad1/5 pathway, rather than the TGF-β1-Smad2/3 pathway. To further validate these results, DMH1 and BMP-7 knockdown were utilized at the cellular level and the results showed that both methods were able to antagonize the effects of kaempferol on the EMT process of NRK-52E cells induced by TGF-β1. 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| subjects | BMP-7 Clear cell-type renal cell carcinoma End-stage renal disease epithelial–mesenchymal transition Fibrosis Flavonoids Kaempferol Kidney diseases Mesenchyme Renal function renal interstitial fibrosis Signal transduction Smad1/5 Smad2 protein Transforming growth factor-b1 |
| title | Kaempferol Protects Renal Fibrosis through Activating the BMP-7-Smad1/5 Signaling Pathway |
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